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Protein

Protein kinase C zeta type

Gene

Prkcz

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro (By similarity).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei281ATPPROSITE-ProRule annotation1
Active sitei376Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri130 – 180Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi258 – 266ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • potassium channel regulator activity Source: Ensembl
  • protein kinase activity Source: MGI
  • protein kinase C activity Source: UniProtKB-EC
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processInflammatory response
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13 3474
ReactomeiR-MMU-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-MMU-5218921 VEGFR2 mediated cell proliferation

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C zeta type (EC:2.7.11.13)
Alternative name(s):
nPKC-zeta
Gene namesi
Name:Prkcz
Synonyms:Pkcz
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:97602 Prkcz

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Endosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557021 – 592Protein kinase C zeta typeAdd BLAST592

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei410Phosphothreonine; by PDPK1 and PI3KBy similarity1
Modified residuei560PhosphothreonineCombined sources1
Modified residuei591PhosphoserineBy similarity1

Post-translational modificationi

CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ02956
PaxDbiQ02956
PRIDEiQ02956

PTM databases

iPTMnetiQ02956
PhosphoSitePlusiQ02956

Expressioni

Gene expression databases

BgeeiENSMUSG00000029053
CleanExiMM_PRKCZ
ExpressionAtlasiQ02956 baseline and differential
GenevisibleiQ02956 MM

Interactioni

Subunit structurei

Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 (By similarity). Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Interacts with PDPK1 (via N-terminal region) (By similarity). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529). Interacts with VAMP2 (PubMed:17313651). Forms a complex with WDFY2 and VAMP2 (PubMed:17313651).By similarity2 Publications

Protein-protein interaction databases

BioGridi202203, 28 interactors
CORUMiQ02956
ELMiQ02956
IntActiQ02956, 16 interactors
MINTiQ02956
STRINGi10090.ENSMUSP00000030922

Structurei

3D structure databases

ProteinModelPortaliQ02956
SMRiQ02956
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 98PB1PROSITE-ProRule annotationAdd BLAST84
Domaini252 – 518Protein kinasePROSITE-ProRule annotationAdd BLAST267
Domaini519 – 590AGC-kinase C-terminalAdd BLAST72

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni79 – 145Interaction with SQSTM1By similarityAdd BLAST67

Domaini

The C1 domain does not bind the diacylglycerol (DAG).
The PB1 domain mediate mutually exclusive interactions with SQSTM1 and PARD6B.By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri130 – 180Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0695 Eukaryota
ENOG410ZMG2 LUCA
GeneTreeiENSGT00820000126964
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiQ02956
KOiK18952
OMAiRCHVLVP
OrthoDBiEOG091G03Q9
TreeFamiTF102004

Family and domain databases

CDDicd00029 C1, 1 hit
cd06404 PB1_aPKC, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR034877 PB1_aPKC
IPR000270 PB1_dom
IPR002219 PE/DAG-bd
IPR012233 PKC
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF00564 PB1, 1 hit
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000554 PKC_zeta, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00666 PB1, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS51745 PB1, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS00479 ZF_DAG_PE_1, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q02956-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPSRTDPKMD RSGGRVRLKA HYGGDILITS VDAMTTFKDL CEEVRDMCGL
60 70 80 90 100
HQQHPLTLKW VDSEGDPCTV SSQMELEEAF RLVCQGRDEV LIIHVFPSIP
110 120 130 140 150
EQPGMPCPGE DKSIYRRGAR RWRKLYRANG HLFQAKRFNR GAYCGQCSER
160 170 180 190 200
IWGLSRQGYR CINCKLLVHK RCHVLVPLTC RRHMDSVMPS QEPPVDDKND
210 220 230 240 250
GVDLPSEETD GIAYISSSRK HDNIKDDSED LKPVIDGVDG IKISQGLGLQ
260 270 280 290 300
DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE
310 320 330 340 350
KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE
360 370 380 390 400
EHARFYAAEI CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE
410 420 430 440 450
GLGPGDTTST FCGTPNYIAP EILRGEEYGF SVDWWALGVL MFEMMAGRSP
460 470 480 490 500
FDIITDNPDM NTEDYLFQVI LEKPIRIPRF LSVKASHVLK GFLNKDPKER
510 520 530 540 550
LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ TLPPFQPQIT DDYGLDNFDT
560 570 580 590
QFTSEPVQLT PDDEDVIKRI DQSEFEGFEY INPLLLSAEE SV
Length:592
Mass (Da):67,682
Last modified:July 27, 2011 - v2
Checksum:i690AD891C25BC311
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti197D → G in AAA39983 (PubMed:1487145).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94632 mRNA Translation: AAA39983.1
AL670413, AL670227 Genomic DNA Translation: CAM20048.1
AL670227, AL670413 Genomic DNA Translation: CAM20648.1
CH466594 Genomic DNA Translation: EDL15000.1
CCDSiCCDS19026.1
PIRiJC1480
RefSeqiNP_032886.2, NM_008860.3
UniGeneiMm.28561

Genome annotation databases

EnsembliENSMUST00000030922; ENSMUSP00000030922; ENSMUSG00000029053
GeneIDi18762
KEGGimmu:18762
UCSCiuc008wdc.2 mouse

Similar proteinsi

Entry informationi

Entry nameiKPCZ_MOUSE
AccessioniPrimary (citable) accession number: Q02956
Secondary accession number(s): A2AD76
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 189 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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